Finding Breast Cancer Cure Has Price

May 14, 1992|By Jean Latz Griffin, Public health writer.

Over the next five years, as 16,000 women take part in a study of whether tamoxifen can prevent breast cancer, researchers hope to prevent 62 cases of breast cancer and 52 heart attacks. But they acknowledge they probably will cause 38 cases of uterine cancer and 3 deaths attributable to blood clots.

In the years following the trial, they probably will prevent many cases of osteoporosis in older women and save many from broken hips.

But, if studies in rats hold true in humans, they may also have triggered a few additional cases of liver cancer. And depending upon how tamoxifen affects cholesterol in premenopausal women, there may be an unknown number of additional heart attacks.

To the researchers, and to the thousands of women signing up for the study around the country, those look like good odds.

Every study of a potentially helpful medication has risks, for those who receive the drug and those in the control group who receive a placebo. The risks in the tamoxifen study are not greater than those in most clinical trials, according to the oncologists and surgeons in the study.

But to critics, including the National Women`s Health Network, the risks outweigh the benefits for many of the women who are likely to participate.

They question the wisdom of giving to healthy women a drug that can have serious side effects, such as cancer and blood clots.

And they are concerned that most of what is known about tamoxifen, which has been used for more than 20 years to treat breast cancer and prevent its recurrence, comes from studies of women who had undergone the hormonal changes involved with menopause.

Both sides agree that little is known about the effects of the drug on young, healthy women whose bodies are still producing abundant estrogen and who have not suffered from or have been treated for cancer.

To researchers, that is one of the reasons the study is needed. To the study`s critics, that is a major danger for unsuspecting women who may let their fears of getting breast cancer blind them to other dangers.

At least one research center in Chicago, the University of Illinois Hospital, struggled long and hard before deciding to join the study, then did so only after it had reworded the proposed consent form to ensure that women knew what they were getting into.

``We were the most worried about the lack of knowledge about the effect of tamoxifen on premenopausal women,`` said one hospital administrator, who was involved in the discussions on whether to do the study but asked not to be named.

The university`s Institutional Review Board, which reviewed the study`s ethics and its scientific validity, was concerned that premenopausal women should not be led to believe that tamoxifen would definitely protect them from cardiovascular disease, said Dr. Michael Mullane, a tamoxifen researcher associated with the University of Illinois Hospital and the Illinois Cancer Council.

``There is no guarantee for premenopausal women,`` Mullane said. ``And when you administer a drug to healthy women, you have to weigh the toxicities differently than when you are using it to treat someone who already has cancer.``

Also, because women in the study cannot take estrogen-replacement therapy, they should be warned that if they are given a placebo, ``they will forgo five years of estrogen (which can reduce the likelihood of osteoporosis or heart disease),`` Mullane said. ``If they feel strongly about that, they should not sign up.``

Although tamoxifen, like estrogen-replacement therapy, does lower the unhealthy cholesterol and prevents osteoporosis by maintaining bone mass in post-menopausal women, there is no evidence that it will protect against cardiovascular disease in women still producing their own estrogen.

``It is possible that tamoxifen could actually cause more heart attacks in premenopausal women because they are hormonally different,`` said Dr. Adriene Fugh-Berman, a physician and member of the board of the Women`s Health Network, a Washington-based non-profit group. ``We don`t want to get the public into the mind-set of trading one disease for another.``

The study will include 16,000 women. Half will receive tamoxifen for five years and half a placebo.

Interest in the trial has been overwhelming. In Chicago, the cancer hot line providing information for the study took 400 calls the first day after the announcement and 300 the second day, the most business it has ever had, Mullane said.

About 165 women have called the University of Chicago Hospitals, said Dr. Monica Morrow, director of the breast program there and one of the principal investigators of tamoxifen research in Chicago.

``Most of the callers are highly educated women, 40 to 45 years old, who have several other risk factors,`` Morrow said. ``Some have been advised to have both their breasts removed to avoid cancer. When you think about that, the risks of tamoxifen are put in perspective.``

All women older than 60 are eligible for the study, because the risk of breast cancer increased with age. The women`s health network disagrees with researchers that just being 60 years old is enough of a risk to take part in the study.

Younger women are eligible if they have other risk factors, such as a mother or sister with breast cancer. The younger the woman the more risk factors she will need to be eligible.

Fugh-Berman said the health network also objects to the assumption in the study that it is more acceptable to get endometrial cancer than breast cancer. But Morrow defends that tradeoff because endometrial cancer is less common, more easily detected and more curable than breast cancer.